Cardiac Arrhythmia Treatments

Learning Objectives

• Drug classes used to treat arrhythmias are categorized by the Vaughan Williams classification
• Drug classes work differently, and have their own mechanisms of action in treating arrhythmias
• Drugs commonly used to treat arrhythmias have specific indications and side effects
• Catheter and device-based treatments also have specific indications for treating arrhythmias

Back to Basics

• Modifying the action potential can elicit an anti-arrhythmic effect

Automaticity of Cardiac Cells

• Cells of the specialized conducting system possess intrinsic automaticity, acting as pacemaker cells
• Under pathologic conditions, cells outside the conduction system may acquire automaticity

Determinants of Cell Firing Rate

• Three variables affect firing rates
• Slope of phase 4 spontaneous depolarization
• Maximum diastolic potential
• Threshold potential

Triggered Automaticity

• Early during Phase 3 of the action potential
• Can occur when the action potential duration increases due to genetic or drug-induced causes
• Drugs like lidocaine that shorten the action potential duration are effective against tachyarrhythmias from this mechanism
• Late during phase 3 or early phase 4
• Action potential is nearly or fully repolarized at this point
• Associated with high intracellular Calcium concentrations due to digitalis toxicity or excessive catecholamine stimulation
• Triggered impulse leads to rapid depolarizations and tachyarrhythmias

The Vaughan Williams Classification

• Drug classes may have overlapping pharmacological effects
• Anti-arrhythmic drugs have a narrow therapeutic window, with potential for both anti- and pro-arrhythmic effects
• Non-cardiac side effects occur

Class I – Na+ Channel Blockers

• Subdivided into IA, IB, and IC
• Drugs bind to open or inactivated Na+ channels, exhibiting "use-dependent channel block"
• The more frequently channels activate, the greater degree of block
• Enables the drug to block rapidly depolarizing cells, but not normal heart rhythm

Class IA

• Block sodium channels and affect phase 0 of the action potential
• Have an effect on potassium channels, therefore prolonging @Tinterval
• Certain drugs in this class also block K+ channels
• Quinidine: Rarely used due to non-cardiac side effects like GI issues and hearing loss

Class IB

• Affect sodium channels
• Decrease phase 0 upstroke and shorten phase 3 repolarization which shortens the duration of the action potential
• Selectively bind to inactivated Na+ channels
• Preferentially block depolarized cells like those in ischemia, such as lidocaine used to treat ventricular arrhythmias during ischemia/post MI

Class IC

• Affect sodium channels
• Have a minimal effect on the action potential duration or the ventricular effective refractory period
• Treat atrial fibrillation with flecainide or propafenone
• These drugs are generally contraindicated in ischemic heart disease or heart failure

Class II – Beta Blockers

• Affect phase 4
• Slow down pacemaker cells & conduction
• Diminish phase 4 depolarization, reducing automaticity, and prolonging AV conduction
• Cause decreased heart rate (negative chronotropic effect) and contractility (negative inotropic effect)
• Treat both atrial and ventricular arrhythmias
• Examples: bisoprolol, metoprolol, atenolol, esmolol, and propranolol

Class III – K+ Channel Blockers

• Potassium channels blockers
• Prolong QT interval
• Block delayed rectifier K+ channels, reducing K+ during cell repolarization in phase 3
• Prolong phase 3 repolarization
• Amiodarone, Sotalol are examples
• Treat atrial and ventricular arrhythmias
• Amiodarone's non-cardiac side effects: thyroid and lung toxicity, liver toxicity, corneal deposits.

Class IV – Ca2+ Channel Blockers

• Calcium channel blockers
• Used to treat supraventricular, tachycardia
• Slow SA firing & AV node conduction
• Block L-type Ca2+ channels
• Causes a decrease in the rate of phase 4 spontaneous depolarization
• Reduce conduction in Ca2+-dependent tissues (SA and AV nodes), slowing the heart to terminate SVT

Class IV - Verapamil & Diltiazem

• Indications: SVT, reduce ventricular rate with atrial fibrillation/flutter
• ADRs: hypotension, constipation, ankle oedema, dizziness, headache, flushing
• Contraindicated in Wolff-Parkinson-White syndrome because the drugs are ineffective and dangerous in treating ventricular arrhythmias

Adenosine and the Heart

• Binds to type 1 adenosine receptors
• A naturally occurring nucleoside with a short half-life (less than 10 seconds)
• Directly opens potassium channels
• Coupled to G proteins
• Activates potassium channels
• Decreases AV conduction velocity
• Decreases automaticity in the AV node
• Prolongs the refractory period
• Terminates AVNRT/AVRT

Digoxin

• Antiarrhythmic
• Slows down conduction in the AV node
• Blocks the plasma membrane Na+/K+ ATPase
• Cardiac glycoside that increases contraction force and reduces conductivity
• Used to control the ventricular response in atrial fibrillation or flutter for patients who are not very active
• Prolongs effective refractory period and slows conduction
• increases the force of myocardial infarction
• Example of true ionotropic agent
• AV block and arrhythmias are adverse drug reactions
• GI side effects, nausea, diarrhea, and visual changes are also ADRs to Digoxin

Ivabradine

• Acts very selectively on the pacemaker current that is responsible for phase 4 of the heart
• Selectivity inhibits the If current of the sinus node
• Reduces the slow diastolic depolarization phase
• Slows down SA automaticity
• Used to treat inappropriate sinoatrial tachycardia and congestive heart failure

Catheter Ablation

• Heats the pathways to the point where they can't conduct electricity
• Used to treat arrhythmia substrates such as slow pathways, accessory pathways, and pulmonary veins
• Examples of such, WPW syndrome
• Energy sources: radiofrequency and cryoablation

Pacemakers

• Used for Bradycardias
• Alternative to heart blocks where no medication available